{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:09:09Z","timestamp":1791940149977,"version":"4.3.4"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"E3-funded Exeter Centre of Excellence for Diabetes Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Diabetes (regardless of type) and obesity are associated with a range of musculoskeletal disorders. The causal mechanisms driving these associations are unknown for many upper limb pathologies. We used genetic techniques to test the causal link between glycemia, obesity and musculoskeletal conditions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In the UK Biobank\u2019s unrelated European cohort (N\u2009=\u2009379\u200a708) we performed mendelian randomisation (MR) analyses to test for a causal effect of long-term high glycaemia and adiposity on four musculoskeletal pathologies: frozen shoulder, Dupuytren\u2019s disease, carpal tunnel syndrome and trigger finger. We also performed single-gene MR using rare variants in the GCK gene.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Using MR, we found evidence that long-term high glycaemia has a causal role in the aetiology of upper limb conditions. A 10-mmol\/mol increase in genetically predicted haemoglobin A1C (HbA1c) was associated with frozen shoulder: odds ratio (OR) = 1.50 [95% confidence interval (CI), 1.20\u20131.88], Dupuytren\u2019s disease: OR\u2009=\u20091.17 (95% CI, 1.01\u20131.35), trigger finger: OR\u2009=\u20091.30 (95% CI, 1.09\u20131.55) and carpal tunnel syndrome: OR\u2009=\u20091.20 (95% CI, 1.09\u20131.33). Carriers of GCK mutations have increased odds of frozen shoulder: OR\u2009=\u20097.16 (95% CI, 2.93\u201317.51) and carpal tunnel syndrome: OR\u2009=\u20092.86 (95% CI, 1.50\u20135.44) but not Dupuytren\u2019s disease or trigger finger. We found evidence that an increase in genetically predicted body mass index (BMI) of 5\u2009kg\/m2 was associated with carpal tunnel syndrome: OR\u2009=\u20091.13 (95% CI, 1.10\u20131.16) and associated negatively with Dupuytren\u2019s disease: OR\u2009=\u20090.94 (95% CI, 0.90\u20130.98), but no evidence of association with frozen shoulder or trigger finger. Trigger finger (OR 1.96 (95% CI, 1.42\u20132.69) P\u2009=\u20093.6e-05) and carpal tunnel syndrome [OR 1.63 (95% CI, 1.36\u20131.95) P\u2009=\u20098.5e-08] are associated with genetically predicted unfavourable adiposity increase of one standard deviation of body fat.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our study consistently demonstrates a causal role of long-term high glycaemia in the aetiology of upper limb musculoskeletal conditions. Clinicians treating diabetes patients should be aware of these complications in clinic, specifically those managing the care of GCK mutation carriers. Upper limb musculoskeletal conditions should be considered diabetes complications.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ije\/dyad187","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T11:00:19Z","timestamp":1704970819000},"source":"Crossref","is-referenced-by-count":21,"title":["Hyperglycaemia is a causal risk factor for upper limb pathologies"],"prefix":"10.1093","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5105-184X","authenticated-orcid":false,"given":"Harry D","family":"Green","sequence":"first","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ella","family":"Burden","sequence":"additional","affiliation":[{"name":"Shoulder Unit, Princess Elizabeth Orthopaedic Centre, Royal Devon and Exeter Hospital , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Evans","sequence":"additional","affiliation":[{"name":"Shoulder Unit, Princess Elizabeth Orthopaedic Centre, Royal Devon and Exeter Hospital , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kashyap","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew R","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0750-8248","authenticated-orcid":false,"given":"Robin N","family":"Beaumont","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9256-6065","authenticated-orcid":false,"given":"Jessica","family":"Tyrrell","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy M","family":"Frayling","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew T","family":"Hattersley","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A","family":"Oram","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Bowden","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5800-4520","authenticated-orcid":false,"given":"In\u00eas","family":"Barroso","sequence":"additional","affiliation":[{"name":"Department of Clinical and Biomedical Sciences, University of Exeter , Exeter, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Smith","sequence":"additional","affiliation":[{"name":"Shoulder Unit, Princess Elizabeth 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